Dose Selection for DuoBody®-CD40x4-1BB (GEN1042/BNT312) Using a mPBPK/RO Model Leveraging Preclinical and Clinical Data.

ABSTRACT: Optimizing target engagement for bispecific antibodies (bsAbs) is challenging, as bsAbs bind to two different targets in vivo to form a trimolecular complex (trimer), and likely display a bell-shaped concentration-response curve. bsAbs trimer formation is expected to be related to efficacy and safety, and determining the dose level at which it is achieved may support dose selection; however, trimer levels currently cannot be quantified in vivo. GEN1042 (DuoBody®-CD40x4-1BB)-a novel, agonistic bsAb-combines targeting and conditional activation of co-stimulatory molecules CD40 and 4-1BB on immune cells, resulting in enhanced priming and reactivation of tumor-specific immunity. We describe data and models that supported GEN1042 dose selection for expansion, including a minimal physiologically

SUBMITTER: Bajaj G 

PROVIDER: S-EPMC12272312 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature